Experimental allergic enciphalitis (EAE) serves as a model of demyelinating disease of the central nervous system. The disease follows T cell sensitization to myelin basic protein, and is controlled in part by immune response genes in the major histocompatibility complex. We have recently prevented EAE in genetically susceptible mice by in vivo administration of antibodies reactive to products of immune response genes. A monoclonal anti I-A antibody was particularly effective. We propose to study the mechanisms whereby antibodies to producet of immune response genes prebent EAE. The mode of action of these antibodies on the homing of sensitized cells to brain, on the sensitization of T cells by myelin protein laden macrophages, and ont eh induction of suppressor cells to myelin protein will be evaluated. An antiserum directed against I-J determinants, found on suppressor T cells, will be used in vivo to try to induce passive relapsing EAE. Since the I region in mice is comparable to the HLA-D region in humans, the long range possibility exists for the use of this type of therapy in HLA-D linked diseases, like multiple sclerosis. This possibility is enhanced by the observation that in vivo treatment with an anti-I-A antibody in an F(1) hybrid produced haplotype specific suppression. Since individuals are usually heterozygous at the critical HLA locus associated with disease susceptibility, suppression of the haplotype controlling disease susceptibility might attenuate the illness, while leaving the immune system otherwise intact. Such therapy might be feasible with anti-HLA-D antibodies as they become available.